title: Characterization of annexin A1 glycan binding reveals binding to highly sulfated glycans with preference for highly sulfated heparan sulfate and heparin.
abstract: Annexin A1 is a multifunctional, calcium-dependent phospholipid binding protein involved in a host of processes including inflammation, regulation of neuroendocrine signaling, apoptosis, and membrane trafficking. Binding of annexin A1 to glycans has been implicated in cell attachment and modulation of annexin A1 function. A detailed characterization of the glycan binding preferences of annexin A1 using carbohydrate microarrays and surface plasmon resonance served as a starting point to understand the role of glycan binding in annexin A1 function. Glycan array analysis identified annexin A1 binding to a series of sulfated oligosaccharides and revealed for the first time that annexin A1 binds to sulfated non-glycosaminoglycan carbohydrates. Using heparin/heparan sulfate microarrays, highly sulfated heparan sulfate/heparin were identified as preferred ligands of annexin A1. Binding of annexin A1 to heparin/heparan sulfate is calcium- but not magnesium-dependent. An in-depth structure-activity relationship of annexin A1-heparan sulfate interactions was established using chemically defined sugars. For the first time, a calcium-dependent heparin binding protein was characterized with such an approach. N-Sulfation and 2-O-sulfation were identified as particularly important for binding.
authors.affiliation: Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Am Mühlenberg 1, D-14476 Potsdam, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Horlacher
authors.forename: C
authors.initials: C
authors.lastname: Noti
authors.forename: J L
authors.initials: JL
authors.lastname: de Paz
authors.forename: P
authors.initials: P
authors.lastname: Bindschädler
authors.forename: M-L
authors.initials: ML
authors.lastname: Hecht
authors.forename: D F
authors.initials: DF
authors.lastname: Smith
authors.forename: M N
authors.initials: MN
authors.lastname: Fukuda
authors.forename: P H
authors.initials: PH
authors.lastname: Seeberger
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006025:Glycosaminoglycans / Q000737:chemistry / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000378:metabolism*; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D051379:Mice; D046228:Microarray Analysis / Q000379:methods; D009994:Osmolar Concentration; D011134:Polysaccharides / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
chemical_list: D017305:Annexin A1; D002118:Calcium; D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D008024:Ligands; D011134:Polysaccharides; D011994:Recombinant Proteins